This ongoing project is designed to explore the basic defect in cystic fibrosis, to study clinical variability or expression of the disease, detail the many complications, to improve diagnostic testing procedures and to seek a screening test for newborns. This clinic is especially suited for these studies because of the large clinic roster of cystic fibrosis patients (approximately 700) many of whom have been followed for over 20 years. A study of lysosomal enzymes using tissue cultured cells from patients with cystic fibrosis and controls suggests alteration in activity of beta-glucosidase and alpha fucosidase. Studies on the development of secretory capacity in exocrine glands, rat pancreas and parotid continues. It appears that in the rat parotid gland slices appropriately incubated can sustain constant levels of protein synthesis for hours and respond to epinephrine and cyclic AMP with release of stored enzymes and with an increase in rate of protein synthesis. However, protein synthesis and enzyme secretin may be independent. The control of synthesis and secretion in normal secretory tissue must be better understood in order to find the defect in cystic fibrosis. We are hampered in detecting the heterozygote because of our inability to find a reliable, constant, and objective test for the presence of the serum factor first discovered by Spock.